The present invention relates to a process for preparing 10-desacetoxytaxol, 10-desacetoxybaccatin III and derivatives of 10-desacetoxytaxol and 10-desacetoxybaccatin III.
Taxol is a natural product extracted from the bark of yew trees. It has been shown to have excellent antitumor activity in in vivo animal models, and recent studies have elucidated its unique mode of action, which involves abnormal polymerization of tubulin and disruption of mitosis. It is currently undergoing clinical trials against ovarian, breast and other types of cancer in the United States and France and preliminary results have confirmed it as a most promising chemotherapeutic agent. The structure of taxol and the numbering system conventionally used is shown below; this numbering system is also applicable to compounds used in the process of the present invention. ##STR1##
In Colin U.S. Pat. No. 4,814,470, it was reported that a taxol derivative, commonly referred to as taxotere, has an activity significantly greater than taxol. Taxotere has the following structure: ##STR2##
Although taxol and taxotere are promising chemotherapeutic agents, a need remains for additional chemotherapeutic agents. The tetracyclic core of taxol bears a C10 acetoxy substituent and taxotere bears a C10 hydroxy substituent which, if modified, would lead to the preparation of a series of taxol analogs. To date, however, the selective manipulation of the C10 acetoxy and hydroxy groups has presented a formidable problem.